MRD Progress in Newly Diagnosed #Myeloma, Quad Induction Therapy and ASCT |Luciano Costa, MD| #ASH24

I'm Luciano Costa, myeloma physician at University of Alabama at Birmingham, and we're here at the ASH meeting in San Diego. And this meeting I had a chance to present with my colleagues from the Comet Consortium and from UAB on the concept of MRD progression. So how we define progression in multiple myeloma has really based on concepts that are like 20, 30 years old, where most times people wouldn't have a profound response. They still have an M-spike that was detectable, which still have quite a bit of plasma cells in the bone marrow. But the fortunate reality is now most patients go on to achieve a deep remission with initial therapy. And now regimens where 60, 70% of the patients achieve MRD negativity. And those patients are being monitored, among other things, with serial MRD assessment. So it's inevitable that we eventually run into situations where the MRD is climbing. MRD is going from negative to positive or is increasing in number. We really don't have a good guidance of what that means or what to do with that. So we took advantage of our master trial. They used quadruple therapy with autologous transplant and MRD guided treatment cessation, plus a hundred and some odd number of patients from our institutional database who are not on trial but had received quadruple therapy and transplant and were monitored with serial MRD to try to describe what that means. And the good news is few patients develop MRD progression or progression. Out of over 200 patients are 30 with progression and 19 with MRD progression without full-blown progression, as if you will, on a follow-up that is now approaching five years. What we found is that even though most of those patients were on observation by the time of the MRD progression, and despite the fact that we start then on some drugs they had received before, usually Revlimid in combination with Dars-LX or some other combination, it's still there's a very short period of time between MRD progression and full-blown progression. And we also saw that the time until failure of the next therapy or overall survival was very similar among those patients with MRD progression and those who come up with full-blown progression. I think that tells us that in this day and age where most people have deep remission, a rise on MRD by tenfold, which is how we define, is very meaningful. It tells you have disease climbing that has the amount to enough to produce an MSPYC or produce symptoms yet, but that gives an opportunity to intervene. And I would go further to say that's an opportunity to intervene. Of course, that needs to be done on a clinical trial at first, but with drugs that those patients have not seen before, because we saw that the reintroduction of prior agents doesn't seem to really be able to abort or be able to avert that full-blown progression. What happens when a patient receives a therapy they've previously been exposed to but are not refractory to? That's a good possibility, right? The patients would receive a therapy, a drug they have been exposed but are refractory to. And I think we need more numbers and more follow-up to be able to separate them out and see if that's a useful approach. What we have now doesn't seem to be the case, but keep in mind the follow-up is short. In the now new era of myeloma where people are living decades, those who are progressing the first three, four years are still pretty aggressive early progression. So maybe those who are having MRD resurgence on year five, year six, year seven, they might be more amenable to therapy with prior drugs. And for the time being, that's what we're doing. But I think hopefully in the future we will see this notion of MRD progression being accepted as good as evidence of rising disease needing to be suppressed as an increase in MS-Py.